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Many factors contribute to bacterial membrane stabilization, including steric effects between lipids, membrane spontaneous curvature, and the difference in the number of neighboring molecules. This forum provides an overview of the physicochemical properties associated with membrane curvature and how this parameter can be tuned to design more effective antimicrobial peptides., Competing Interests: Declaration of interests C.F-N. provides consulting services to Invaio Sciences and is a member of the Scientific Advisory Boards of Nowture S.L., Peptidus, and Phare Bio. C.F-N. is also on the Advisory Board of the Peptide Drug Hunting Consortium (PDHC). The de la Fuente Lab has received research funding or in-kind donations from United Therapeutics, Strata Manufacturing PJSC, and Procter & Gamble, none of which were used in support of this work. C.F-N. is on the Advisory Board of Cell Reports Physical Science., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The advent of multidrug resistance among pathogenic bacteria has attracted great attention worldwide. As a response to this growing challenge, diverse studies have focused on the development of novel anti-infective therapies, including antimicrobial peptides (AMPs). The biological properties of this class of antimicrobials have been thoroughly investigated, and membranolytic activities are the most reported mechanisms by which AMPs kill bacteria. Nevertheless, an increasing number of works have pointed to a different direction, in which AMPs are seen to be capable of displaying non-lytic modes of action by internalizing bacterial cells. In this context, this review focused on the description of the in vitro and in vivo antibacterial and antibiofilm activities of non-lytic AMPs, including indolicidin, buforin II PR-39, bactenecins, apidaecin, and drosocin, also shedding light on how AMPs interact with and further translocate through bacterial membranes to act on intracellular targets, including DNA, RNA, cell wall and protein synthesis.

Hospital infections allied to bacterial resistance to antibiotics have become a major worldwide problem. In this context, antimicrobial peptides (AMPs) are presented as an alternative in the control of these resistant organisms. Besides antimicrobial effects, these molecules play a crucial role in immunity by acting as immunomodulators. These peptides can activate inflammatory cells to produce pro- and anti-inflammatory mediators. In this study we will show the activity against multi-drug resistant bacteria (MDRB) of two cathelicidins from South American pit vipers Bothrops atrox and Crotalus durissus terrificus, named batroxicidin and crotalicidin. It was observed that both peptides showed activity against MDRB and presented no hemolytic or cytotoxic activity. In addition, the ability of peptides to modulate the production of cytokines TNF-α, IL-10 and IL-6 was analyzed using Raw 264.7 cells in the presence of IFN-γ stimuli, and multi-resistant E. coli and K. pneumoniae antigens. An up-expression or down-expression of TNF-α, as well as the IL-10 mediator, was observed. The cytokine IL-6, on the other hand, presented only a down-regulation for Raw 264.7 cell groups. In conclusion, the results demonstrate that both peptides presented a predominantly proinflammatory characteristic to the inflammatory mediators dosed. Overall, even presenting a proinflammatory characteristic, these peptides are still promising for future research and development of new potential antimicrobial molecules., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Due to the growing concern about antibiotic-resistant microbial infections, increasing support has been given to new drug discovery programs. A promising alternative to counter bacterial infections includes the antimicrobial peptides (AMPs), which have emerged as model molecules for rational design strategies. Here we focused on the study of Pa-MAP 1.9, a rationally designed AMP derived from the polar fish Pleuronectes americanus. Pa-MAP 1.9 was active against Gram-negative planktonic bacteria and biofilms, without being cytotoxic to mammalian cells. By using AFM, leakage assays, CD spectroscopy and in silico tools, we found that Pa-MAP 1.9 may be acting both on intracellular targets and on the bacterial surface, also being more efficient at interacting with anionic LUVs mimicking Gram-negative bacterial surface, where this peptide adopts α-helical conformations, than cholesterol-enriched LUVs mimicking mammalian cells. Thus, as bacteria present varied physiological features that favor antibiotic-resistance, Pa-MAP 1.9 could be a promising candidate in the development of tools against infections caused by pathogenic bacteria.

Unusual methods for specific detection of pathogenic bacteria are becoming key points for control and identification of problems related to health and (bio)safety. In this context, this work aims to propose a new approach for the development of nanostructured biosensors based on carbon nanotubes (CNTs) and antimicrobial peptides for bacterial detection. Firstly, the antimicrobial peptide clavanin A (ClavA) was chemically immobilized on CNTs and surface-immobilized ClavA was used to detect Klebsiella pneumoniae, Enterococcus faecalis, Escherichia coli and Bacillus subtilis in a direct assay format. We used electrochemical impedance spectroscopy technique to evaluate the effectiveness and sensitivity of the ClavA-based biosensors by measuring the modifications in their electrochemical responses before and after incubation in presence of different bacteria concentrations. The biosensor was able to discriminate between bacteria concentrations in the 10(2)-10(6)CFU mL(-1) range. Atomic force microscopy analysis confirmed the biosensor functionality for bacterial recognition. This new sensor system was capable of differentiating between Gram-positive and Gram-negative bacteria, since ClavA showed different affinities toward the pathogenic bacteria species., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Antimicrobial peptides (AMPs), especially antibacterial peptides, have been widely investigated as potential alternatives to antibiotic-based therapies. Indeed, naturally occurring and synthetic AMPs have shown promising results against a series of clinically relevant bacteria. Even so, this class of antimicrobials has continuously failed clinical trials at some point, highlighting the importance of AMP optimization. In this context, the computer-aided design of AMPs has put together crucial information on chemical parameters and bioactivities in AMP sequences, thus providing modes of prediction to evaluate the antibacterial potential of a candidate sequence before synthesis. Quantitative structure-activity relationship (QSAR) computational models, for instance, have greatly contributed to AMP sequence optimization aimed at improved biological activities. In addition to machine-learning methods, the de novo design, linguistic model, pattern insertion methods, and genetic algorithms, have shown the potential to boost the automated design of AMPs. However, how successful have these approaches been in generating effective antibacterial drug candidates? Bearing this in mind, this review will focus on the main computational strategies that have generated AMPs with promising activities against pathogenic bacteria, as well as anti-infective potential in different animal models, including sepsis and cutaneous infections. Moreover, we will point out recent studies on the computer-aided design of antibiofilm peptides. As expected from automated design strategies, diverse candidate sequences with different structural arrangements have been generated and deposited in databases. We will, therefore, also discuss the structural diversity that has been engendered. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides are an abundant group of proteinaceous compounds widely produced in the plant kingdom. Among them, the γ-thionin family, also known as plant defensins, represents one typical family and comprises low molecular mass cysteine-rich proteins, usually cationic and distributed in different plant tissues. Here, we report the purification and characterization of a novel γ-thionin from cowpea seeds ( Vigna unguiculata), named Cp-thionin II, with bactericidal activity against Gram-positive and Gram-negative bacteria. Once the primary structure was elucidated, molecular modelling experiments were used to investigate the multimerization and mechanism of action of plant γ-thionins. Furthermore, Cp-thionin II was also localized in different tissues in cowpea seedlings during germination in contrasting conditions, to better understand the plant protection processes. The use of plant defensins in the construction of transgenic plants and also in the production of novel drugs with activity against human pathogens is discussed. [ABSTRACT FROM AUTHOR]

The gut microbiota presents essential functions in the immune response. The gut epithelium acts as a protective barrier and, therefore, can produce several antimicrobial peptides (AMPs) that can act against pathogenic microorganisms, including bacteria. Several factors cause a disturbance in gut microbiota, including the exacerbated and erroneous use of antibiotics. Antibiotic therapy has been closely related to bacterial resistance and is also correlated with undesired side-effects to the host, including the eradication of commensal bacteria. Consequently, this results in gut microbiota imbalance and inflammatory bowel diseases (IBD) development. In this context, AMPs in the gut epithelium play a restructuring role for gut microbiota. Some naturally occurring AMPs are selective for pathogenic bacteria, thus preserving the health microbiota. Therefore, AMPs produced by the host's epithelial cells represent effective molecules in treating gut bacterial infections. Bearing this in mind, this review focused on describing the importance of the host's AMPs in gut microbiota modulation and their role as anti-infective agents against pathogenic bacteria. [Display omitted] • The gut microbiota presents essential functions in the immune response. • AMPs in the gut epithelium play a restructuring role for gut microbiota. • AMPs modulate the gut microbiota. • Commensal bacteria express AMPs to combat pathogenic microorganisms. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) are molecules with potential application for the treatment of microorganism infections. We, herein, describe the structure, activity, and mechanism of action of RQ18, an α-helical AMP that displays antimicrobial activity against Gram-positive and Gram-negative bacteria, and yeasts from the Candida genus. A physicochemical-guided design assisted by computer tools was used to obtain our lead peptide candidate, named RQ18. This peptide was assayed against Gram-positive and Gram-negative bacteria, yeasts, and mammalian cells to determine its selectivity index. The secondary structure and the mechanism of action of RQ18 were investigated using circular dichroism, large unilamellar vesicles, and molecular dynamic simulations. RQ18 was not cytotoxic to human lung fibroblasts, peripheral blood mononuclear cells, red blood cells, or Vero cells at MIC values, exhibiting a high selectivity index. Circular dichroism analysis and molecular dynamic simulations revealed that RQ18 presents varying structural profiles in aqueous solution, TFE/water mixtures, SDS micelles, and lipid bilayers. The peptide was virtually unable to release carboxyfluorescein from large unilamellar vesicles composed of POPC/cholesterol, model that mimics the eukaryotic membrane, indicating that vesicles' net charges and the presence of cholesterol may be related with RQ18 selectivity for bacterial and fungal cell surfaces. RQ18 was characterized as a membrane-active peptide with dual antibacterial and antifungal activities, without compromising mammalian cells viability, thus reinforcing its therapeutic application. These results provide further insight into the complex process of AMPs interaction with biological membranes, in special with systems that mimic prokaryotic and eukaryotic cell surfaces. [Display omitted] • RQ18 is a membrane-active peptide with dual antibacterial and antifungal activities. • The peptide displays a lower affinity for zwitterionic membranes. • RQ18 exhibited no hemolytic or cytotoxic properties toward mammalian cells. [ABSTRACT FROM AUTHOR]

Abstract: Cowpea crops are severely attacked by Callosobruchus maculatus, a Coleopteran that at the larval stage penetrates into stored seeds and feeds on cotyledons. Cowpea weevil control could be based in utilization of bacteria and fungi to reduce pest development. Entomopathogenic fungi, such as Metarhizium anisopliae, are able to control insect-pests and are widely applied in biological control. This report evaluated ten M. anisopliae isolates according to their virulence, correlating chitinolytic, proteolytic and α-amylolytic activities, as well proteomic analysis by two dimensional gels of fungal secretions in response to an induced medium containing C. maculatus shells, indicating novel biotechnological tools capable of improving cowpea crop resistance. [Copyright &y& Elsevier]

Biofilm-related infections represent an enormous clinical challenge nowadays. In this context, diverse studies are underway to develop effective antimicrobial agents targeting bacterial biofilms. Here, we describe the antibacterial and anti-biofilm activities of a short, cationic peptide named R5F5, obtained from sliding-window analysis based on a peptide (PcDBS1R5) derived from Plasmodium chabaudi. Ten fragments were generated (R5F1 to F10) and submitted to initial antibacterial assays against Pseudomonas aeruginosa. As a result, R5F5 showed the highest antimicrobial activity. We therefore carried out further antibacterial and anti-biofilm assays against P. aeruginosa and Klebsiella pneumonia e carbapenemase-producing bacterial strains. R5F5 revealed selective anti-biofilm activity, as the peptide inhibited >60% biofilm formation in all cases from 8 to 64 μg·mL−1. Moreover, R5F5 was not hemolytic against mice erythrocytes at 640 μg mL−1. Cytotoxic effects on human lung fibroblast cells were not detected at 160 μg·mL−1. Structural studies revealed that R5F5 presents random coil conformations in water and 50% 2,2,2-trifluoroethanol (TFE)/water (v/v), whereas amphipathic, extended conformations were observed in contact with sodium dodecyl sulfate (SDS) micelles. Thus, here we report a novel peptide with selective anti-biofilm activity against susceptible and resistant bacterial strains, with no toxicity toward mammalian cells and that adopts a stable structure in anionic environment. Image 1 • R5F5 is the most active sliding-window fragment from PcDBS1R5. • R5F5 presents selective antibiofilm activity Gram-negative bacteria. • The fragment R5F5 is non-toxic toward mammalian cells (dose-dependent). • In the presence of SDS micelles R5F5 adopts a stable, amphipathic arrangement. [ABSTRACT FROM AUTHOR]